Pre-mitotic genome re-organisation bookends the B cell differentiation process
- Author(s)
- Chan, WF; Coughlan, HD; Zhou, JHS; Keenan, CR; Bediaga, NG; Hodgkin, PD; Smyth, GK; Johanson, TM; Allan, RS;
- Details
- Publication Year 2021-02-26,Volume 12,Issue #1,Page 1344
- Journal Title
- Nature Communications
- Abstract
- During cellular differentiation chromosome conformation is intricately remodelled to support the lineage-specific transcriptional programs required for initiating and maintaining lineage identity. When these changes occur in relation to cell cycle, division and time in response to cellular activation and differentiation signals has yet to be explored, although it has been proposed to occur during DNA synthesis or after mitosis. Here, we elucidate the chromosome conformational changes in B lymphocytes as they differentiate and expand from a naive, quiescent state into antibody secreting plasma cells. We find gene-regulatory chromosome reorganization in late G1 phase before the first division, and that this configuration is remarkably stable as the cells massively and rapidly clonally expand. A second wave of conformational change occurs as cells terminally differentiate into plasma cells, coincident with increased time in G1 phase. These results provide further explanation for how lymphocyte fate is imprinted prior to the first division. They also suggest that chromosome reconfiguration occurs prior to DNA replication and mitosis, and is linked to a gene expression program that controls the differentiation process required for the generation of immunity.
- Publisher
- NPG
- Research Division(s)
- Bioinformatics; Population Health And Immunity; Immunology
- PubMed ID
- 33637722
- Publisher's Version
- https://doi.org/10.1038/s41467-021-21536-2
- Open Access at Publisher's Site
https://doi.org/10.1038/s41467-021-21536-2- NHMRC Grants
- NHMRC/1125436, NHMRC/1054925, NHMRC/1124081, NHMRC/1100451, NHMRC/1158531,
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- Refer to copyright notice on published article.
Creation Date: 2021-03-09 01:36:42
Last Modified: 2021-03-09 01:48:03